BRC-BIO: Interrogating Extracellular Vesicle Biogenesis Through Substrate-Associated Signals

Harvey Mudd College, Claremont CA

Investigators

Abstract

Cell communication is necessary for the healthy function of living organisms. Cells communicate by directly touching or by sending materials out to other cells. One of the ways that cells send materials is via extracellular vesicles. Extracellular vesicles are collections of nucleic acids, proteins, and lipids that are held together by a protective envelope. When cells receive these extracellular vesicles and unpack the vesicle’s contents, they change their behavior. Even though this form of communication is important, the nature of vesicle formation and selection of their contents is not well understood. The goal of this project is to enhance understanding by determining the factors that cause cells to produce vesicles and the factors that influence what materials are packaged inside of them. Understanding extracellular vesicle formation and packaging has the potential to result in new medical interventions. This work will be undertaken with secondary students and undergraduates. The research experience will equip them with the training and professional development necessary to create knowledge for this project. The outcomes of student engagement in this research will also expand understanding, by generating outcomes and new research questions in vesicle biogenesis. The specific knowledge that will be enhanced by this project is the role played by integrin-substrate interactions on extracellular vesicle biogenesis, subpopulation production, and selective cargo packaging. In this work, engineered hydrogel substrates will be deployed to engage integrins expressed by astrocytes, which represent a compelling system for studying extracellular vesicle biogenesis. Because their function is coupled to environmental cues, the ability of these astrocytes to respond to extracellular signals is necessary for the fitness, survival, and healthy function of the nervous system. This project seeks to determine how cell engagement with integrin-specific peptides influences the extracellular vesicle production and to provide an experimental platform that can be modified to decipher the signals and mechanisms that promote extracellular vesicle production. An understanding of the mechanisms underlying extracellular vesicle biogenesis will afford new insights into the fundamentals of cell-cell communication and provide new avenues for creating vesicle-based therapeutics. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.